Autism And Immunology

Tony Hermawan

Pendahuluan
Autisme adalah salah satu bentuk penyakit yanng tergolong dalam gangguan pervasif. Berasal dari autos diri sendiri menunjukkan gejala hidup dalam dunia sendiri Autisme adalah gangguan perkembangan pervasif pada anak yang ditandai dengan adanya gangguan dan keterlambatan dalam bidang kognitif, bahasa, perilaku, komunikasi dan interaksi sosial.

 Autism is a complex, developmental disability that is evident within the first 3 years of life. It is a behaviorally defined syndrome that is recognized by difficulties in communication, social interaction and perceptual organization (pattern of behavior) . Symptoms vary in degree of severity, from mild to severe impairments.

Etiologi
Evironmental factor : congenital rubella infection anticonvulsants and antiemetics taken during pregnancy, perinatal hypoxia postnatal infections such as encephalitis Genetic ?

Sistim Neuromunologi
Kelainan sistim imun pada autisme dihubungkan dengan adanya antibodi reaktif pada SSP yang mengakibatkan terjadinya kerusakan jaringan neuron Paparan sistim imun pada periode kritikal perkembangan sist imun menyebabkan terjadinya autisme

Sistem imun dan sistem Saraf

Keduanya merupakan suatu sistem yang bekerja menyampaikan sinyal melalui pelepasan mediator kimiawi seperti neuropeptida, neurothropin dan sitokinin. Banyak peptida yang sama berperan dalam kedua sistim tersebut.

Traditional view of Autism

Autism is a group of behaviors caused by some defective gene or genes which cause structural changes in the brain. We cant fix brain abnormalities that you are born with, so other than behavioral therapies, there isnt anything that will improve the childs level of functioning.

Immune and Nervous systems

Communicate with chemical messages Interact with each other

The Ideal Immune System

Recognize all foreign organisms.
Bacteria, viruses, parasites (fungi,worms)

Efficiently and rapidly destroy invaders. Prevent a second infection with the same microbe (have a memory). Never cause damage to self.

Cytokines the Language of the Immune System

Chemical messages that are the main communication system between cells of the immune system (and other systems especially the nervous system).

Cytokines the Language of the Immune System

Can be divided several ways: Th1 (adaptive/memory, cell mediated): IL-2, IFN- Th2 (adaptive/memory, antibodies):IL-4, IL-5, IL-13, IL10,TGF- Innate: TNF-, IL-1, IL-6, IL-12 Pro-inflammatory: TNF-, IL-1, IL-6 Anti-inflammatory: TGF-, IL-10 Regulatory: IL-10, IL-12,TGF-

Immunopathology in autism
Dysregulation of immunity in autistic children leads to all four problems: Deficiency / dysfunction Hypersensitivity / allergy Autoimmunity

Inflammation

Immune Abnormalities in Autism

Abnormal immune systems have been found in about 20-70% of patients with autism in a wide variety of studies, depending on which part of the immune system is examined. Studies are generally small with not-well-characterized children or are limited to a single subgroup so it is hard to draw firm conclusions. Nearly every study finds that some children have poor T regulatory function Many studies find that ASD children have low-normal immunoglobulins (IgG, IgM, IgA) and/or low T cell numbers and/or low-normal functioning and/or low and poorly functional Natural Killer cells ; a subset of children have true immunodeficiency. Some children have low serum IgA, predisposing them to respiratory and GI infections.

Blood (serum) findings in ASD

Some children have allergy (atopy) with high levels of IgE. Traditional IgE allergies can be measured either by blood testing (RAST) or by skin prick testing. It is well documented that in neurotypical children, untreated allergies cause poor memory and concentration as well as poor sleep.

Blood (serum) findings in ASD

A child on the autism spectrum with recurrent infections deserves an immune evaluation for immunodeficiency A child on the autism spectrum with eczema, chronic nasal symptoms, asthma, significant GI symptoms, or recurrent respiratory infections deserves an allergy evaluation for IgE inhalant and food allergies.

 There is a tendency towards a positive family history of autoimmunity in families Rheumatoid Arthritis, Thyroiditis - with an ASD child, and a genetic tendency towards autoimmune disorders as well. Many, many types of autoantibodies (against self tissues) have been found in ASD children but the significance of the many types of anti-brain antibodies is not clear.

GI Tract - Mucosal findings

Gut inflammation in some children Abnormal lymphocyte profiles: lots of T cells present where none should be. Abnormal cytokine profiles: proinflammatory with lots of TNF- and too little regulatory IL-10

Immune Reactions to Food

Immune cells from autistic children with GI symptoms showed strong pro-inflammatory response and a reduced ability to switch off the immune response compared to normal children. Immune reactivity to milk and wheat common with or without GI symptoms. Soy and corn next most common. Still no test or good predictors (although a few children did have IgE antibodies which can be measured) - elimination and challenge best. Yeast (Candida albicans) overgrowth also found in the stools of some children

Autism spectrum disorders and allergy: observation from a pediatric allergy/immunology clinic Harumi Jyonouchi Pediatrics, University of Medicine and Dentistry of New Jersey (UMDNJ)

Immunity, neuroglia and neuroinflammation in autism (vargas et al)

prenatal viral infections might damage the immature immune system and induce viral tolerance (Stubbs & Crawford, 1977) decreased production of immunoglobulins or B and T-cell dysfunction (Warren et al.,1986)

Immunity, neuroglia and neuroinflammation in autism (vargas et al)